Arachidonic acid metabolism in a cloned strain of rat pituitary tumor cells: correlation between 15 hydroxyeicosatetraenoic acid release and the prolactin secretory process.

We investigated the involvement of arachidonic acid metabolites in basal and thyrotropin releasing hormone (TRH) stimulated prolactin release by GH3 cells, a cloned strain of rat pituitary tumor cells. GH3 cells spontaneously released 9 and 15 HETEs and the 15 HETE release was greater than that of 9 HETE. When the cells were challenged by 10(-5) M AA, they were able to produce 5, 9, 12 and 15 HETEs. 10(-6) M TRH only stimulated the release of the two metabolites synthesized by the basal cells (15 and 9 HETEs). This release depended on the length of stimulation by TRH. When both AA and TRH were added, there was an increase in 15 and 9 HETE production. In all cases, more 15 HETE was released than other metabolites. In dose-response studies using TRH concentrations of 10(-6) M to 10(-12) M, the highest level of 9 HETE release was obtained at 10(-11) M TRH and the highest release of 15 HETE was at 10(-9) M TRH. PRL secretion by GH3 cells challenged by TRH showed the same pattern as 15 HETE release, and the correlation between PRL and 15 HETE was significant (p less than 0.001). These data indicate that 15 HETE is the lipoxygenase metabolite released in the largest amounts by GH3 cells and suggest some physiological interaction between 15 HETE and TRH in the control of PRL secretion.